Carbocisteine, chemical name S-(carboxymethyl)-L-cysteine (carboxymethylcysteine, CMC), was firstly developed in 1961 by a French company Joullie and was clinically applied. As a mucolytic drug, carbocisteine can affect the secretion from bronchial glands, promote the secretion of low-viscosity salivary mucin and reduce the production of high-viscosity fucomucin. It can also be directly applied to disulfide bonds of mucin, so that mucin molecules are cracked and the sputum viscosity is reduced to help cough out the sputum. The medicine can improve the clearance rate of mucosal cilia and reduce airway hyperresponsiveness. Carboxymethyl of the CMC can be easily removed after entering the body to form a cysteine, and the sulfydryl contained therein can interact with electrophilic groups such as reactive oxygen species (ROS) to exert a direct antioxidant effect. In addition, the cysteine is also a precursor of glutathione (GSH), which can be resynthesized into a GSH with biological activity, so as to increase the concentration of the GSH in vivo, and exert an indirect antioxidant effect. CMC has good oral absorption, and quick effect, obvious curative effect observed 4 hours later after it is taken, and it can be applied for the treatment of thick sputum and expectoration difficulties caused by chronic bronchitis, emphysema, chronic obstructive pulmonary disease (COPD), bronchial asthma and the like. Chronic obstructive pulmonary disease (COPD) is characterized by airway obstruction which is incompletely reversible and progressively developed. According to the World Health Organization, COPD, among the causes of death due to diseases worldwide, ranks only next to heart disease, cerebrovascular disease and acute lung infection, while ranking the fourth together with AIDS. On a global scale, there are more than 600 million patients suffering from the disease, among which there are up to 27 million patients suffering from chronic obstructive pulmonary disease in China each year. At present, COPD is mainly treated by medicine to relieve symptoms of the patients, and reduce acute exacerbation of the disease.
In 2006, a Japanese scholar Yasuda H conducted a randomized double-blind trial. The results showed that for the patients suffering from COPD, the frequency of catching colds is reduced and the acute exacerbation of COPD is relieved after taking CMC in large doses and for a long time (1500 mg/d, 12 months) (Yasuda H, Yamaya M, Sasaki T, et al. Carbocisteine reduces frequency of common colds and exacerbations in patients with chronic obstructive pulmonary disease. J Am Geriatr Soc. 2006; 54 (2): 378-80). In 2007, a Japanese scholar Tatsumi K conducted a multi-center parallel randomized trial for which 142 patients suffering from COPD were chosen. The results showed that the patients suffering from COPD are prevented from acute COPD after taking CMC in large doses and for a long time (1500 mg/d, 12 months), and St Goorge's questionnaire and other studies showed that the life quality of the patients can be improved (Tatsumi K, Fukuchi Y. Carbocisteine improves quality of life in patients with chronic obstructive pulmonary disease. J Am Geriatr Soc. 2007; 55 (11): 1884-6.). In 2008, Zhong Nanshan et al. studied and found that taking carbocisteine in large doses and for a long time (1500 mg/d, 12 months) can better prevent acute chronic obstructive pulmonary disease, with an annual acute morbidity per person being reduced by 24.5%. The curative effect of carbocisteine is close to the international standard of inhaled corticosteroids combined with long-acting agonists or long-acting anticholinergic medicines; and the curative effect thereof is not affected by the severity of the chronic obstructive pulmonary disease and combined medication, the treatment costs can be reduced by 85% as compared with the international standard of inhalation therapy. The results of this study showed that carbocisteine has a very good prospect for the treatment of chronic obstructive pulmonary disease (Jin-Ping Zheng, Nan-Shan Zhong, etc. Effect of carbocisteine on acute exacerbation of chronic obstructive pulmonary disease (PEACE Study): a randomized placebo-controlled study. Lancet, 2008; 371:2013-18).
As an expectorant, carbocisteine is commonly produced and used in China. However, as there are two carboxyl groups which are acidic in the structure of carbocisteine, the digestive tract is irritated by the medicine, thus causing adverse reactions such as stomach discomfort, nausea, vomiting, gastrointestinal hemorrhage and so on. If the medicine is taken for a long time, the gastrointestinal mucosa is likely damaged, resulting in hemorrhage, ulcers and even perforation and other serious side effects. Meanwhile, it is clearly noted in medicine instructions of “patients in active period of gastrointestinal ulcer are forbidden to use the medicine.” Therefore, searching for safe and effective carbocisteine alternatives is of great significance for the treatment of COPD and other diseases.